DESCRIPTION Adapted from applicant's abstract): The precise organization of individual neurons into neural circuits is essential for all neural functions. There is increasing evidence that such debilitating mental diseases as schizophrenia and autism may result from failure of neural circuits to develop properly. A common feature of neural circuits is the convergence of several inputs onto a single target. This convergence requires that a neuron not only find and synapse with the proper postsynaptic cell, but also appropriately share this target cell with other inputs. In some cases, the functioning of the circuit critically depends on the precise connection of the presynaptic cell onto a specific sub-region of the postsynaptic neuron, for example, onto a single dendritic branch or onto the initial segment of the axon. Studying this development in a simple nervous system not only allows one to learn the mechanisms involved, but also may eventually allow one to interpret the functional consequences of inappropriate development. The experiments proposed are designed to characterize the connection between a subset of neurons involved in a specific behavior, the local bending reflex, in the medicinal leech. Specifically, the connection from each of two pairs of excitatory interneurons onto a shared postsynaptic motor neuron will be studied. The precise location of each connection will be identified by photoablation of branches and subsequent intracellular electrical recording of the presynaptic and postsynaptic cells. The time at which the connection first develops will be determined by using paired electrical recordings at several different embryonic ages. Finally, the role of interactions among presynaptic neurons, as well as between the presynaptic neuron with specific postsynaptic branches, in generating precise connections, will be assessed by ablating entire presynaptic cells or individual postsynaptic branches during development, before any connections are made.